tbuckley/cabot-search huggingface dataset:
Abstract 5986: WAVE2/EGF signaling and miR29 regulates WAVE2 to promote tumor growth and metastasis in triple negative breast cancer
Authors: Priyanka S. Rana, Wei Wang, Akram Alkrekshi, Vesna Markovic, Khalid Sossey-Alaoui
Journal: Cancer Research (2022)

Abstract Breast cancer is the most frequently diagnosed malignancy in women and is one of the leading causes of death due to cancer invasion, metastasis, and resistance to therapies. Among its variants, triple-negative breast cancer (TNBC) is considered the most aggressive due to its early age of diagnosis, invasive and metastatic properties with poor prognosis. TNBC is a type of breast cancer that lacks expression of the receptors that are commonly found in this type of cancer (estrogen, progesterone, and HER2), which makes it a more difficult target for treatment. Cancer invasiveness and metastasis are known to be promoted by increased cell motility and upregulation of the Wiskott-Aldrich syndrome protein (WASP) and WASP family verprolin-homologous protein (WAVE) - WAVE1, WAVE2, and WAVE3. While the contribution of WAVE2 to cancer progression is well documented, the WAVE2-mediated regulation of TNBC oncogenic properties is still under investigated. In this study, we show that WAVE2 plays a significant role in TNBC development, progression, and metastasis. To investigate this notion, we used CRISPR/Cas9 gene editing to successfully inhibit WAVE2 expression in several TNBC cell lines. In vitro, loss of WAVE2 expression inhibited 3D tumorsphere formation and invasion of TNBC cells. In vivo, in mouse models for TNBC, loss of WAVE2 inhibited tumor growth and metastasis. Mechanistically, we show that the WAVE2-mediated modulation of the oncogenic behavior of TNBC cells is in part due to its phosphorylation downstream of EGF. At the post transcriptional level, we found WAVE2 expression to be regulated by miR29. Together, our findings identify a novel post-translational WAVE2/EGF oncogenic signaling axis, along with a post-transcriptional regulatory axis downstream of miR29, which together regulate the oncogenic activity of WAVE2 in TNBC and open a new therapeutic strategy for the treatment of TNBC. Citation Format: Priyanka S. Rana, Wei Wang, Akram Alkrekshi, Vesna Markovic, Khalid Sossey-Alaoui. WAVE2/EGF signaling and miR29 regulates WAVE2 to promote tumor growth and metastasis in triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5986.
Circulating tumor DNA in B-cell lymphoma: technical advances, clinical applications, and perspectives for translational research
Authors: Eliza M. Lauer, Jurik Mutter, Florian Scherer
Journal: Leukemia (2022)

Abstract Noninvasive disease monitoring and risk stratification by circulating tumor DNA (ctDNA) profiling has become a potential novel strategy for patient management in B-cell lymphoma. Emerging innovative therapeutic options and an unprecedented growth in our understanding of biological and molecular factors underlying lymphoma heterogeneity have fundamentally increased the need for precision-based tools facilitating personalized and accurate disease profiling and quantification. By capturing the entire mutational landscape of tumors, ctDNA assessment has some decisive advantages over conventional tissue biopsies, which usually target only one single tumor site. Due to its non- or minimal-invasive nature, serial and repeated ctDNA profiling provides a real-time picture of the genetic composition and facilitates quantification of tumor burden any time during the course of the disease. In this review, we present a comprehensive overview of technologies used for ctDNA detection and genotyping in B-cell lymphoma, focusing on pre-analytical and technical requirements, the advantages and limitations of various approaches, and highlight recent advances around improving sensitivity and suppressing technical errors. We broadly review potential applications of ctDNA in clinical practice and for translational research by describing how ctDNA might enhance lymphoma subtype classification, treatment response assessment, outcome prediction, and monitoring of measurable residual disease. We finally discuss how ctDNA could be implemented in prospective clinical trials as a novel surrogate endpoint and be utilized as a decision-making tool to guide lymphoma treatment in the future.
Risk assessment with gut microbiome and metabolite markers in NAFLD development
Authors: Howell Leung, Xiaoxue Long, Yueqiong Ni, Lingling Qian, Emmanouil Nychas, Sara Leal Siliceo, Dennis Pohl, Kati Hanhineva, Yan Liu, Aimin Xu, Henrik B. Nielsen, Eugeni Belda, Karine Clément, Rohit Loomba, Huating Li, Weiping Jia, Gianni Panagiotou
Journal: Science Translational Medicine (2022)

A growing body of evidence suggests interplay between the gut microbiota and the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, the role of the gut microbiome in early detection of NAFLD is unclear. Prospective studies are necessary for identifying reliable, microbiome markers for early NAFLD. We evaluated 2487 individuals in a community-based cohort who were followed up 4.6 years after initial clinical examination and biospecimen sampling. Metagenomic and metabolomic characterizations using stool and serum samples taken at baseline were performed for 90 participants who progressed to NAFLD and 90 controls who remained NAFLD free at the follow-up visit. Cases and controls were matched for gender, age, body mass index (BMI) at baseline and follow-up, and 4-year BMI change. Machine learning models integrating baseline microbial signatures (14 features) correctly classified participants (auROCs of 0.72 to 0.80) based on their NAFLD status and liver fat accumulation at the 4-year follow up, outperforming other prognostic clinical models (auROCs of 0.58 to 0.60). We confirmed the biological relevance of the microbiome features by testing their diagnostic ability in four external NAFLD case-control cohorts examined by biopsy or magnetic resonance spectroscopy, from Asia, Europe, and the United States. Our findings raise the possibility of using gut microbiota for early clinical warning of NAFLD development.
Abstract 5425: Quantitative determination of fibroblast growth factor receptor inhibitor-AZD4547 using HPLC analysis in a mouse model of ultraviolet B (UVB)-induced skin carcinogenesis
Authors: Rema Anisha Kandula, Katherine Claire Babin, Brian Latimer, Kenneth Mc Martin, Lauren Linquest, Tara Moore-Medlin, Megha A. Thakur, Alok R. Khandelwal, John DiGiovanni, Cherie-Ann O. Nathan
Journal: Cancer Research (2022)

Abstract Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer affecting more than two million Americans annually. Cumulative sun exposure plays a leading role in the pathogenesis of cSCC. In our previous studies, topical application of Fibroblast growth factor receptor (FGFR) inhibitor AZD4547 was associated with a significant reduction in Ultraviolet B-induced (UVB)-induced acute skin changes such as epidermal hyperplasia and hyperproliferation. Further, chronic, topical application of AZD4547 was associated with significant inhibition in UVB-induced tumor incidence and multiplicity. Unfortunately, oral administration of FGFR inhibitors in clinical trials for solid tumors is associated with notable side effects such as hyperphosphatemia, diarrhea, decreased appetite, fatigue, and liver dysfunction. Therefore, our objective was to investigate whether topical administration of AZD4547 could potentially circumvent systemic absorption, leading to a low toxicity profile. Accordingly, mice were topically administered AZD4547 (400ug/200ul acetone) followed by exposure to UVB three times a week for two weeks. Blood was collected at the end of the study. AZD4547 was extracted using methanol extraction and concentrated using a Savant SpeedVac system. Samples were reconstituted in 25% acetone/75% water solution and analyzed using Reverse-phase HPLC (Shimadzu) with a Zorbax Eclipse C18 3.5-µm 4.6x100mm analytical column operated at ambient temperature and gradient elution using trifluoroacetic acid (TFA) (Mobile A) and 0.1% TFA in Acetonitrile. Data from HPLC analysis demonstrated non-appreciable absorption of AZD4547 (blood levels only from 108-358nM) suggesting that the topical application of AZD4547 was not systemically absorbed and the effect of treatment was restricted to the local skin tissue. Based on the efficacy and low systemic absorption profile, AZD4547 could potentially be utilized as a topical agent to both prevent and treat UVB-induced cSCC. Citation Format: Rema Anisha Kandula, Katherine Claire Babin, Brian Latimer, Kenneth Mc Martin, Lauren Linquest, Tara Moore-Medlin, Megha A. Thakur, Alok R. Khandelwal, John DiGiovanni, Cherie-Ann O. Nathan. Quantitative determination of fibroblast growth factor receptor inhibitor-AZD4547 using HPLC analysis in a mouse model of ultraviolet B (UVB)-induced skin carcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5425.
Abstract 2220: Immunohistochemical detection of prostate cancer heterogeneity by using ETS and PTEN monoclonal antibodies
Authors: Cara Schafer, Denise Young, Yingjie Song, Jiji Jiang, Albert Dobi, Gyorgy Petrovics, Bettina F. Drake, Gregory T. Chesnut, Isabell A. Sesterhenn, Shyh-Han Tan
Journal: Cancer Research (2022)

Abstract The multifocality and highly variable molecular pathology of prostate cancer are underlying features of this clinically heterogeneous disease. Most patients harbor multiple molecularly distinct cancer foci at diagnosis that likely arose as independent clones. There is a critical need for molecular biomarkers that can distinguish the multifocality and inter-focal heterogeneity of tumors and help stratify patients for treatment. PTEN loss and ETS gene rearrangements are among the most prevalent genomic alterations in prostate carcinogenesis. The detection of both ERG overexpression and PTEN protein loss by immunohistochemistry (IHC) have proven to be reliable substitutes for detecting genomic alterations by fluorescence in situ hybridization (FISH) assay. We developed monoclonal antibodies against ETV1 and ETV4 and evaluated their performance in prostate cancer specimens. The expression of ETV1, ETV4, were examined in relation to ERG and loss of PTEN expression in TMAs constructed from primary prostate cancer specimens of two independent patient cohorts. The first TMA was constructed from multiple 1 mm cores representing distinct tumor focus from multifocal tumors from 50 African American (AA) and 50 Caucasian American (CA) men. The second was constructed from a single 2 mm core of individual tumors from an independent cohort of 152 AA and 304 CA men. We present results on the expression of each protein biomarker in the context of patient race and their association with clinico-pathologic features, together with concurrence or mutual exclusiveness for each event. These results support the application of ETS monoclonal antibodies in IHC assays to detect prostate cancer tumor heterogeneity and to identify subsets of prostate cancer. Citation Format: Cara Schafer, Denise Young, Yingjie Song, Jiji Jiang, Albert Dobi, Gyorgy Petrovics, Bettina F. Drake, Gregory T. Chesnut, Isabell A. Sesterhenn, Shyh-Han Tan. Immunohistochemical detection of prostate cancer heterogeneity by using ETS and PTEN monoclonal antibodies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2220.
Abstract 1200: COSMIC cancer mutation census: Classifying somatic coding variants by their potential to drive cancer
Authors: Zbyslaw Sondka, Bhavana Harsha, Helder Pedro, Nidhi Bindal Dhir, Charlie Hathaway, Sumodh Nair, Doron Sondheimer, Simon A. Forbes
Journal: Cancer Research (2022)

Abstract Somatic mutations accumulate in cells throughout their life. Most of them do not bring any negative effect. However, certain mutations change protein behaviour, structure, or level of expression. More importantly, some mutations are known to initiate and drive oncogenic transformation. These mutations often make good therapeutic targets but recognising this small subset in a cancer sample is a major challenge. The average cancer cell carries a life-long baggage of somatic mutations, and the mutational process is sped up in these cells through genomic instability (one of the hallmarks of cancer). As a result, there are hundreds of thousands of variants of unknown significance identified through sequencing of cancer DNA. COSMIC Cancer Mutation Census (CMC) answers this challenge by identifying coding mutations with a potential to drive cancer. This is achieved by combining manually curated information regarding cancer genes and genetic variants with data on variant frequencies in cancer and non-cancer populations, and algorithmic evaluation of variant significance. It applies a simple and transparent set of rules to the whole set of coding mutations in COSMIC to identify variants with the highest potential of clinical relevance. In current version (v95, November 2021) the CMC describes 4.7 million somatic variants and segregates them into four tiers. Tier 1 is the highest confidence set. This set includes 1558 mutations that are found in Cancer Gene Census genes and are also described as pathogenic in cancer by ClinVar. Tiers 2 and 3 contain variants with less extensive evidence of involvement in carcinogenesis. The dN/dS algorithm is used to include variants that are under positive selection in cancer cells. Finally, mutations without evidence for driving cancer are classified as Tier 4. In addition to this classification, CMC integrates and presents the information used to prioritise variants, including their frequencies in various cancer types (COSMIC), germline frequencies (gnomAD), ClinVar annotations, dN/dS analysis results, and nucleotide and amino acid conservation. Data can be accessed and scrutinised through a dedicated website at https://cancer.sanger.ac.uk/cmc. Citation Format: Zbyslaw Sondka, Bhavana Harsha, Helder Pedro, Nidhi Bindal Dhir, Charlie Hathaway, Sumodh Nair, Doron Sondheimer, Simon A. Forbes. COSMIC cancer mutation census: Classifying somatic coding variants by their potential to drive cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1200.
Abstract 5921: Machine learning based detection of pancreatic tumors using the Dxcover® cancer platform
Authors: Alexandra Sala, James M. Cameron, Cerys A. Jenkins, Hugh Barr, Loren Christie, Justin J. Conn, Thomas (Jeff) R. Evans, Dean A. Harris, David S. Palmer, Christopher Rinaldi, Ashton G. Theakstone, Matthew J. Baker
Journal: Cancer Research (2022)

Abstract Pancreatic cancer is the 7th most deadly cancer worldwide with over 460,000 victims per year. In the current diagnostic pathway, carbohydrate antigen (CA) 19-9 serum test is the first method used for detection of pancreatic cancer; although, with poor positive predictive values reported, it cannot provide certain information about the presence of a pancreatic tumor or other surrounding tumors in symptomatic patients. Attenuated total reflection - Fourier transform infrared spectroscopy (ATR-FTIR) has demonstrated exceptional potential in human blood serum analysis for cancer diagnostics and its implementation in the clinical environment could represent a significant step forward in the early detection of pancreatic cancer. This proof-of-concept study was focused on the discrimination between both cancer versus healthy control samples, and cancer versus symptomatic control samples from patients with comorbidities and/or confounding diseases. The study aimed to investigate the use of the Dxcover® cancer platform as a novel approach for pancreatic cancer detection. Various machine learning algorithms were applied to discriminate between cancer (n=100) and healthy control samples (n=100), achieving results amounting to a sensitivity of 91.0 ± 5.6%, specificity of 87.6 ± 5.8%, and accuracy of 89.3 ± 3.8% with partial least squares-discriminant analysis (PLS-DA). Moreover, an area under the curve (AUC) equal to 0.9536 was obtained through receiving operating characteristic (ROC) analysis. The same algorithms were also applied to discriminate between cancer (n=35) and symptomatic control samples (n=35) achieving a balanced sensitivity and specificity over 75% with an AUC of 0.8436. Both discriminations underwent bootstrapping validation and were proven statistically significant. Herein, we present these results and demonstrate that ATR-FTIR spectroscopic analysis of serum is a cost-effective, minimally invasive, highly sensitive and specific test for detection of pancreatic cancer. Citation Format: Alexandra Sala, James M. Cameron, Cerys A. Jenkins, Hugh Barr, Loren Christie, Justin J. Conn, Thomas (Jeff) R. Evans, Dean A. Harris, David S. Palmer, Christopher Rinaldi, Ashton G. Theakstone, Matthew J. Baker. Machine learning based detection of pancreatic tumors using the Dxcover® cancer platform [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5921.
Abstract LB034: Evaluation of a novel single-cell RNA sequencing methodology for use in clinical trial settings
Authors: David Corney, Yang Han, Yu Qiu, Yongjun Fan, Michael Stephens, Andrea O'Hara, Laure Turner, Christopher Mozdzierz, Haythem Latif, Ginger Zhou
Journal: Cancer Research (2022)

Abstract Bulk RNA sequencing (RNA-seq) is regularly employed for transcriptional profiling but provides only a snapshot of the average population. Particularly when studying disease, understanding differences in diverse cells is essential thus single-cell resolution is a necessity due to significant cellular heterogeneity. High-throughput droplet- and microfluidic-based approaches for performing single-cell RNA-seq (scRNA-seq) are invaluable techniques for uncovering changes in cells such as differential gene expression and epigenetic states in cancer research. A challenge for scRNA-seq, however, is sample preparation as typically tissues must be processed immediately after collection. We and others have reported alternative approaches to stabilize samples prior to analysis such as cryopreservation of cells and tissues and methanol-based fixation of cells. However, the inclusion of these approaches is still limited in many settings due to the challenging logistics involved in sample collection. To further broaden the ability of researchers to deploy scRNA-seq, we report our experiences from testing a pre-commercial workflow developed by 10x Genomics to resolve these sample management limitations. The use of paraformaldehyde (PFA) to fix samples at the collection site allows samples to be transported to remote laboratories for downstream processing without sacrificing integrity or data quality. This advance has enabled new possibilities for sample accessibility, throughput, and batched analysis in basic and translational research settings. Furthermore, this approach also allows for analysis of transcriptome-wide gene expression at high sensitivity with simultaneous cellular readouts. Here we report a case study comparing the PFA method to standard approaches, and highlight advantages and potential applications previously not possible with reported sample preparation strategies. Citation Format: David Corney, Yang Han, Yu Qiu, Yongjun Fan, Michael Stephens, Andrea O'Hara, Laure Turner, Christopher Mozdzierz, Haythem Latif, Ginger Zhou. Evaluation of a novel single-cell RNA sequencing methodology for use in clinical trial settings [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB034.
Abstract 435: COVID-19 &amp; cancer prevention in Texas: Reasons cited for HPV vaccination hesitancy and refusal during the pandemic
Authors: Onyema Chido-Amajuoyi, Mala Pande, Robert Yu, Sanjay Shete
Journal: Cancer Research (2022)

Abstract Background: HPV vaccination is highly effective at preventing several squamous cell carcinomas. However, the uptake of this vaccine remains sub-optimal in the US, with further exacerbation of this poor uptake during the pandemic. This study aims to describe changes and barriers to HPV vaccination during the COVID-19 pandemic as observed by healthcare professionals (HCPs) in the state of Texas. Methods: Data for this study were derived from a statewide cross-sectional survey of HCPs in the state of Texas (n=1283). Survey instruments were developed at MD Anderson Cancer Center, and reviewed by its IRB. Survey frequencies were used to estimate for the proportional distribution of changes as observed by HCPs regarding HPV vaccination i) uptake ii) hesitancy and iii) refusal during the COVID-19 pandemic. HCPs who observed increases in vaccination hesitancy or refusal, were then asked for the reasons cited by their patients. Survey frequencies were then used to determine the proportional distribution of the reasons cited for HPV vaccination hesitancy and refusal during the pandemic. All statistical analysis were conducted using R version 3.5.2. Results: Overall, 730 HCPs responded to the study questions of interest. A predominant proportion of respondents were employed in group practice settings or university teaching/affiliated hospitals. About 20% of HCPs in Texas observed decreases in HPV vaccination uptake. Observed increments in HPV vaccination hesitancy and refusal were reported by 17.1% and 14.8% of HCPs, respectively. Among HCPs who observed increased hesitancy and refusal, difficulties in scheduling clinic visit during the pandemic and fear of contracting corona virus during the clinic visit were the most cited reasons. Discussion: Findings of the index study suggest that the COVID-19 pandemic has had a negative impact on HPV vaccination in Texas. Results identify perceived barriers to HPV vaccination unique to the pandemic. With the pandemic still ongoing, amid the emergence of novel strains with heightened virulence, despite the presence of highly effective FDA-approved vaccines, findings of this study provides useful insight for public health interventions, as well as to guide physician-patient interactions around HPV vaccination. Citation Format: Onyema Chido-Amajuoyi, Mala Pande, Robert Yu, Sanjay Shete. COVID-19 &amp; cancer prevention in Texas: Reasons cited for HPV vaccination hesitancy and refusal during the pandemic [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 435.